The primary objective of the trial was to assess the safety and tolerability of avelumab. Secondary objectives included assessment of the best overall response, progression-free survival (PFS), and overall survival (OS), as well as of the association between PD-L1 expression on tumor cells and immune cells within the tumor and the clinical activity of avelumab.

Patients were eligible if they had confirmed recurrent or refractory stage III or IV ovarian cancer that had progressed within 6 months of platinum-based therapy or after subsequent therapy for previously relapsed disease.

Other eligibility criteria included adequate performance status, estimated life expectancy of at least 3 months, measurable disease per RECIST v1.1 criteria, and availability of fresh biopsy or archived tumor material for analysis of PD-L1 expression using a proprietary immunohistochemistry assay at defined cut-off levels of expression. However, patients were not selected for PD-L1 expression.

Patients received avelumab 10 mg/kg as a 1-hour intravenous infusion every 2 weeks until progression, unacceptable toxicity, or withdrawal from the study. Efficacy was assessed every 6 weeks according to RECIST, and the collection of blood for CA125 testing was required. BRCA 1/2 mutational status was determined retrospectively from medical records.

The 124 patients in the study received a median of 6 doses (range, 1 to 26) for a median duration of treatment of 12 weeks (range, 2 to 54 weeks). Median follow-up was 12.4 months, and 17 patients remained on treatment at the time of analysis.

Treatment-related adverse events (TRAE) occurred in 66.1% of patients. Of these, 8 (6.5%) were grade ≥3. TRAE resulted in discontinuation in 10 patients, and included grade 3 colitis, myositis, arthritis, edema, and grade 4 hyperglycemia (1 patient each), as well as grade ≥3 immune-mediated TRAEs in 2 patients. There were no treatment-related deaths.

Partial response was seen in 12 patients for an objective response rate of 9.7%. The disease control rate (rate of response or best overall response of stable disease) was 54%. Responses were seen in 6 patients by the time of first assessment at week 6; 10 patients had responses by week 10. Median PFS was 11.3 months, and median OS was 10.8 months.

Of the 72 patients evaluable for CA 125, concentration increased in 81.9% and decreased in 18.1%; 1 of the 10 patients with a response by RECIST had a decrease in CA 125 concentration from baseline.

The overall response rate (ORR) was 16% in patients with wild-type BRCA; no responses occurred in patients with mutated BRCA. The disease control rate (responses plus stable disease) was 48% and 11.1% in patients with wild-type BRCA and mutated BRCA, respectively.

There were 74 specimens (59.7%) evaluable for PD-L1 expression. There were no statistically significant differences in ORR, median PFS, or median OS between patients with PD-L1 positive or negative tumors.
Single-agent avelumab had acceptable safety with some clinical activity in heavily pretreated patients with ovarian cancer in the largest study of anti-PD(L)1 agents in this patient population to date. No relationship between the potential biomarkers tested, including PD-L1 level, CA 125 concentration, or BRCA mutational status and response to avelumab was seen.

Lead author Mary L. Disis, MD, University of Washington, Seattle commented, “Although avelumab response rates are less than what we see in other inflamed tumors like melanoma or squamous cell non–small cell lung cancer, I think when you look at the patient population, [which is] very heavily pretreated, having a 10% to 14% response rate, with a few deep and very durable responses, sets the stage of avelumab as backbone to immunotherapy, as something to be brought in to cause inflammation in this low inflamed cancer, ovarian cancer.”